A final common pathway for depression: implications for therapy.

Depression in humans and animal models has been found to be accompanied by a hypoactivity of brain regions involved in positively motivated behavior together with a hyperactivity in regions involved in stress responses. Both sets of changes are reversed by diverse antidepressant treatments. It has been proposed that this neural pattern underlies the symptoms common to most forms of depression, which are the loss of positively motivated behavior and the increase in stress. The present paper discusses how this framework can organize diverse findings on the multiple factors associated with this disorder. The hypothesis suggests new therapeutic strategies involving treatment with low-dose corticosteroids to suppress the stress network or with antagonists of α1A- and agonists of α1B-adrenoceptors to disinhibit or activate the positive motivational network, respectively.